The long term objective is to better understand the immunopathogenesis of an AIDS-like mouse model termed the RCN-BM5 system. The virologically well-defined RCN-BM5 retrovirus(es), in the remarkably short latency of 2-4 weeks in 100% of inoculated, adult, immunocompetent C57BL/6 mice, induces a profound B cell lymphoproliferation/lymphoma as well as a profound immunodeficiency of T and B cells. The biologic characteristics of this profound lymphoproliferation/immunosuppression are essentially unknown. It is therefore the specific aim of this proposal to better characterize the target cells that support retroviral infection and replication in diseased C57BL/6 mice. Using a powerful experimental design, which combines immunophenotype with MCF- retroviral gene expression (using sensitive in-situ hybridization techniques), we will determine the phenotypic and morphologic nature of retrovirally-infected cells in lymphoid tissues (primarily lymph nodes and spleen) from diseased mice over a rigorous time course. Since our preliminary studies indicate that cells of the macrophage/dendritic series are infected early in the course of disease, we are testing the important hypothesis that subsequently activated T and/or B lymphocytes are susceptible to MCF-retrovirus infection with time. It should be stressed that this combined immunomorphologic and molecular approach will be performed by an experienced hematopathologist in the context of the preserved histopathology and microanatomy of diseased lymphoid tissues. Furthermore, since we are hypothesizing that an immunologically activated cascade is occurring with progressive retroviral infection, an additional specific aim is to determine which immunomorphologic types of retrovirally-infected cells are expressing genes coding for specific cytokines and/or other important gene products, which may be contributing to the pathogenesis of the profound B cell lymphoproliferation/lymphoma. Using in situ hybridization techniques, we will specifically determine the precise immunomorphologic cell types, which are expressing genes (at the mRNA level) coding for a variety of monokines (IL-1) and lymphokines (IL-2, gamma interferon, BCDF(s), and BCGF(s)) as well as for genes coding for MHC Class II molecules and IL-2 receptors. In addition to the evaluation of histologically-preserved tissues, we will confirm the presence of mRNA expression for cytokines, other relevant genes, and MCF retrovirus on FACS-sorted, phenotypically-defined cell types from the same diseased lymphoid tissues.